Lysosomal Diseases

Lysosomal storage Disorders (LSD) are a group of approximately 45 rare genetic disorder caused by deficiency of certain enzymes in certain compartments of the cells. All LSDs share a common pathogenesis: a genetic defect in one or more specific lysosomal enzymes, activator protein or membrane protein, resulting in deficient enzymatic activity. In other words, when the lysosome does not function normally, excess products destined for breakdown and recycling is stored in the cell.

The lysosome itself was discovered in 1955 and by 1960 its role in cellular digestion was well understood. Pompe disease was the first to be formally diagnosed. By 1970s the scientific community had recognized many more LSDs and categorized them based on the type of enzymatic defect and/or stored substrate product.

The symptoms of Lysosomal Storage Disease vary, depending on the particular disorder and other variables like the age of onset, and can be mild to severe. They can include developmental delay, movement disorders, seizures, dementia, deafness and/or blindness. Some people with Lysosomal Storage Disease have enlarged livers (hepatomegaly) and enlarged spleens (splenomegaly), pulmonary and cardiac problems, and bones that grow abnormally. A patient with LSD not only develops physical deformation in cell structures throughout the body, but these cells often die resulting in a wide variety of clinical symptoms. If diagnosed late and/or left untreated patients are at risk of developing significant, irreversible damage and loss of body functions, anf life-threatening complications.

Treatment

There are no cures for lysosomal storage diseases and treatment is mostly symptomatic, although bone marrow transplantation and enzyme replacement therapy (ERT) have been successful in some cases.   In addition, umbilical cord blood transplantation is being performed at specialized centers for a number of these diseases.  In addition, substrate reduction therapy, a method used to decrease the accumulation of storage material, is currently being evaluated for some of these diseases. Furthermore, chaperone therapy, a technique used to stabilize the defective enzymes produced by patients, is being examined for certain of these disorders.  Gene therapy involves replacing the patient’s mutated gene with a normal copy to allow proper enzyme production.  However, it is still in pre-clinical (animal studies) and much research is needed.

Diagnosis

The majority of the patients are initially screened by enzyme assay, which is the most efficient method to arrive at a definitive diagnosis.  In some families where the disease-causing mutation(s) is known and in certain genetic isolates, mutation analysis may be performed.  In addition, after a diagnosis is made by biochemical means, mutation analysis may be performed for certain disorders.


 

 

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